Molecular mimicry is defined as the theoretical possibility that sequence or structure similarities between foreign and self-peptides are sufficient enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. The prerequisite for molecular mimicry to occur is thus the sharing of the immunodominant epitope between the pathogen and the immunodominant self sequence that is generated by a cell or tissue. The mechanism by which pathogens have evolved, or obtained by chance, similar amino acid sequences or the homologous three-dimensional crystal structure of immunodominant epitopes remains a mystery (Wikipedia, the free encyclopedia).
An autoimmune disease occurs when a host fail to recognize self antigens as “self”. Growth in the study of autoimmunity has resulted in more and more people being diagnosed with an autoimmune disease which affects approximately 1 in 31 people within the general population. However, rapid diagnosis and effective prevention and treatment of autoimmune diseases have been very limited due to the unknown causes and pathogenesis mechanisms of these diseases. In recent years, there has been tremendous growth in the study of the several different ways in which autoimmunity can occur; one of which is molecular mimicry.
An infectious disease is a clinically evident disease of humans or animals. Information collected by the World Health Organization on global deaths shows that worldwide mortality due to infectious diseases is as high as 25.9% of all deaths, or 14.7 million deaths in 2002. The top three infectious disease killers which caused 58% of deaths caused by infectious disease were mainly virus related infections such as lower respiratory infections, HIV/AIDS and diarrheal diseases. The most effective medical approaches to viral infections so far are vaccinations. Other significantly effective medicines for viral infections are limited. Virus entry into the host cells by binding receptor or co-receptor (host cell surface factors that bind to native virions). The receptors and co-receptors are major determinants of viral tropism, limiting the host range, and probably the nature of the age-dependent (affect only infant or young children). The tissue distribution of receptors and co-receptors in part determines the symptoms of infections. Therefore, precise knowledge of the viral receptors and co-receptors will help to develop new antiviral and vaccine strategies. Such studies have been largely left uninvestigated due to the lack of a simple and efficient technique to identify and purify receptors and co-receptors of infectious agents. Molecular mimicry can be a useful tool for this application.
Cancer is a disease characterized by a population of cells that grow and divide without respect to normal limits, invade and destroy adjacent tissues, and may spread to distant anatomic sites through a process called metastasis. Cancer causes about 13% of all deaths. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. The role of molecular mimicry in the pathogenesis of infection-related cancers has never been explored.
To determine which epitopes are shared between pathogen and self, large protein databases are used. The largest protein database in the world, known as the SWISS-PROT database, has shown reports of molecular mimicry becoming more common with expansion of the database. Due to the amino acid variation between different proteins, molecular mimicry should not happen from a probability standpoint. The possibility exists, then, for variability within amino acid sequence, but similarity in three-dimensional structure between two peptides can be recognized by T or B cell clones. This, therefore, uncovers a flaw of such large databases. They may be able to give a hint to relationships between epitopes, but the important three-dimensional structure cannot yet be searched for in such a database.